Alcoholism is a complex disease and anti-relapse treatments should recognize this. For example, depression is a frequent precipitant of relapse (1) and is the most common co-morbid psychiatric disorder in alcoholism. An anti-relapse agent with antidepressant properties might therefore be valuable, specifically for this large subpopulation. In this regard, the extracts of "St John's Wort", (Hypericum perforatum) that are effective treatments for clinical depression (see 2) also inhibit alcohol consumption in several animal models (e.g. (3). Like antidepressants, H perforatum extracts contain serotonin re-uptake inhibitors (SRIs), but (less wellknown) constituents also bind to NMDA receptors (NMDARs), opioid receptors (ORs), GABAA receptors, and corticotrophin releasing factor receptors (CRFRs). This is a unique pharmacological spectrum, and is potentially valuable because all of these are molecular targets for anti-relapse agents, with NMDARs and ORs being the targets for acamprosate and naltrexone respectively. Native Hypericum species and geneticallymodified H perforatum lines share these actions in greater or lesser degree (Preliminary studies) and their relative importance could therefore be assessed using these species or lines. However, in this "fast-track" STTR, the aim is simply to identify those novel Hypericum extracts that are of most potential value in alcoholism. In phase 1, the focus will be on pharmacological standardization of extracts using molecular and cellular screens developed for evaluation of synthetic anti-relapse medications. In phase 2, evaluation will continue in simple animal screens of alcohol dependence and/or depression, and different models of alcohol consumption. The prediction is that some extracts will be more effective than others, and that this can be related to the pharmacological activity they contain. The resulting stronger Intellectual Property (compared to known active H perforatum extracts) will make these more commercially attractive as medications for this specific use. In phase 3 the objective (with a major pharmaceutical partner) will be to commercialize extracts, or active components, as treatments for prevention of relapse in alcoholic patients with co-morbid depression. [unreadable] [unreadable] [unreadable]